NSAIDs: Medicines involved

Last updated: October 08, 2018

There are many NSAIDs available on prescription, and ibuprofen and naproxen can be purchased over the counter. Differences in anti-inflammatory activity between NSAIDs are small, but patients can vary in their response to treatment – people who don't respond adequately to one may respond better to another.
If you'd like to see a list of all the NSAIDs currently available in the UK please click here (click again to close)
Non-selective NSAIDs:
Aceclofenac Dexibuprofen DexketoprofenDiclofenac
Etodolac  FenoprofenFlurbiprofenIbuprofen 
IndometacinKetoprofenMefenamic acid Meloxicam 
Nabumetone Naproxen PiroxicamSulindac
TenoxicamTiaprofenic acidTolfenamic acid
– – – – – – – – – – – – – –

We noted earlier that NSAIDs work by inhibiting the enzyme cyclooxygenase (COX). Actually there are two forms of that enzyme: COX-1 promotes homeostatic functions like protecting the upper GI tract from damage, whilst COX-2 generates the prostaglandins responsible for inflammation. Conventional NSAIDs inhibit both forms of COX, but coxibs are more selective for COX-2. Studies analysing the relative GI toxicity of different anti-inflammatory medicines suggest that coxibs are associated with a reduced risk of bleeding compared to most non-selective NSAIDs.

One recent meta-analysis suggested that, compared to people not using NSAIDs, the relative risk of developing upper GI complications was 1.45 with celecoxib, and about 4.1 for naproxen and indometacin. The same meta-analysis suggested that ibuprofen at doses less than 1200 – 1800mg per day posed a relative risk of 2.15 whereas for higher doses this was 4.22.

Another meta-analysis gave a relative risk of 1.81 for the coxibs as a class, 3.97 for ibuprofen 2400mg per day, and 4.22 for naproxen 1000mg per day.

The bottom line is that coxibs have greater GI safety than NSAIDs like ibuprofen, naproxen and indometacin, but lower ibuprofen doses (less than 1200 – 1800mg per day) seem safer than higher doses.

Although the risk may be less for certain medicines or doses, upper and lower GI complications are associated with all NSAIDs and coxibs, and appropriate awareness and precaution is needed when prescribing any of them. Oral and rectal NSAID formulations can both cause GI damage, but topical formulations (e.g. ibuprofen gel) do not pose a significant risk because the amount of NSAID reaching the general circulation is so small.

Cardiovascular complications

A complicating factor is that as a class, the coxibs have been shown to confer an increased risk of adverse cardiovascular effects compared to non-selective NSAIDs such as naproxen. However, diclofenac has a higher cardiovascular risk profile too, hence the MHRA recommends that diclofenac, like coxibs, is contraindicated for people with ischaemic heart disease, peripheral arterial disease, cerebrovascular disease, or congestive heart failure (grades II to IV). Topical formulations of NSAIDs are, once again, not a significant risk for systemic cardiovascular effects.

An evidence-based assessment by NICE in 2018 concluded that naproxen (up to 1000mg per day), and ibuprofen (up to 1200mg per day), have the most favourable thrombotic cardiovascular safety profiles of all the NSAIDs.

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